The research objectives are to clarify the relative roles of blood- brain barrier mechanisms and brain tissue (intra- and extracellular, neurons and glia) exchanges in the regulation of brain acid-base balance and potassium balance and the effects of these processes on the control of breathing. Preliminary studies in K ion depleted rats have uncovered alterations in CSF HCO minus over 3 homeostasis, brain tissue K ion regulation, and the control of breathing. These animals along with normal rats will be used in the following studies. 1. Clarification of the changes in brain tissue (K ion) and its distribution in intracellular compartments (glia and neurons) as well as extracellular compartment (CSF) in normal and K ion depleted rats. 2. Brain tissue buffer capacity and a derived intracellular pH will be evaluated in normal and K ion depleted rats in vivo and the buffer capacity of isolated populations of neurons and glial cells will be evaluated in vitro. 3. A proposed integrating hypothesis for CSF HCO minus over 3 homeostasis that states CSF HCO minus over 3 is dependent on tissue PCO2 and on arterial (HCO minus over 3) only when the latter is above a "threshold" value will be evaluated in K ion depleted and control rats. 4. The abnormal breathing pattern in K ion depleted rats will be related to pHe, PHi, and PHi, for isolated neurons and glia as derived from 1, 2, and 3. The effects of K ion depletion after vagotomy will determine if a low K ion effect on breathing frequency and tidal volume exists independent of the vagus.